Regioselective Chemoenzymatic Synthesis of Ganglioside Disialyl

ABSTRACT: A novel chemoenzymatic approach for the synthesis of disialyl tetrasaccharide epitopes found as the terminal oligosaccharides of GD1α, GT1aα, and GQ1bα is described. It relies on chemical manipulation of enzymati-cally generated trisaccharides as conformationally con-strained acceptors for regioselective enzymatic α2−6-sialylation. This strategy provides a new route for easy access to disialyl tetrasaccharide epitopes and their derivatives. Sialic acids are common terminal residues on the glycanchains of various cell-surface glycoproteins and glycolipids. These unique nine-carbon monosaccharides on the outermost position of cell-surface glycoconjugates play important roles in many physiological and pathological processes.1 For example, the disialyl tetrasaccharide 1α (Figure 1) with an α configuration at the reducing end is found in the O-glycan